The present invention relates to a novel method of treatment. More particularly, the present invention relates to a novel method for preventing or treating hepatic diseases.
Most particularly, the present invention relates to the surprising and unexpected effect of certain prostaglandins and prostaglandin analogs in treating liver diseases.
Liver diseases take a number of forms including jaundice, hepititis, cirrhosis, circulatory disorders, fatty liver, amyloid disease, neoplasms, and biliary disorders. See, The Merck Manual, 12th Edition, 762-788 (1972).
Among the most frequently occurring liver diseases are cirrhosis of the liver and fatty liver disease. Cirrhosis of the liver is caused from a variety of sources including alcoholism, prolonged biliary tract obstruction, submassive hepatic necrosis of viral hepititis, malnutrition, hemochromatosis, hepatolenticular degeneration (Wilsons Disease), congestive heart failure, and syphilis.
Two types of cirrhosis are known. Portal cirrhosis (also known as Laennec's, fatty, nutritional, or alcoholic cirrhosis) is characterized by uniform diffused small modules, fine fibrosis, and pseudolobule formation, accompanied by extensive fatty vacuolization. This is a more common form of cirrhosis. Postnecrotic cirrhosis (also known as post-hepatic, toxic, healed yellow atrophy, or macronodular cirrhosis) is characterized by irregular large nodules, broad bands of scar tissue, and preservation of some normal liver architecture. These two forms of cirrhosis may be variations of a single disease process or different entities. See The Merck Manual, supra.
Fatty liver disease is caused by excessive fat intake, ingestion of intoxicants, (e.g., alcohol, carbon tetrachloride, and chloroform), chronic infections, metabolic disorders, and anemias. The symptoms are not specific and cannot be distinguished from those of other chronic diseases such as cirrhosis, chronic passive congestion, amyloidosis, and leukemia.
The treatment for fatty liver disease and cirrhosis generally consists of a protein rich diet supplemented by vitamins and the like. Strict abstinence from alcohol is essential.
Pharmacological agents which prevent necrotic changes in cells are known as cytoprotective agents. Numerous gastrointestinal cytoprotective effects of the prostaglandins are known. See for example U.S. Pat. No. 4,083,998 (Robert, "Treatment of Inflammatory Disease of the Mammalian Large Intestine with Cytoprotective Prostaglandins"), issued April 11, 1978, U.S. Pat. No. 4,081,553 (Robert, "Cytoprotective Prostaglandins for Use in Intestinal Diseases"), issued March 28, 1978, and U.S. Pat. No. 4,097,603 (Robert, "Gastric Cytoprotection with Non-Antisecretory Doses of Prostaglandins"), issued June 27, 1978. Agents which are specific for the reduction of liver damage are referred to herein as hepatocytoprotective agents.
The prostaglandins are derivatives of prostanoic acid. A trivial system of nomenclature has been devised, which classifies the prostaglandins according to the substituents on the cyclopentane ring. See, N. A. Nelson, Journal of Medicinal Chemistry, 17:911 (1974). For a further discussion of the prostaglandins, see Bergstrom, et al., Pharmacol. Rev. 20:1 (1968).